[Show abstract][Hide abstract] ABSTRACT: Bariatric surgery (BS) has become more frequent among women of child-bearing age. Data regarding the underlying maternal and perinatal risks are scarce. The objective of this nationwide study is to evaluate maternal and perinatal outcomes after BS.
[Show abstract][Hide abstract] ABSTRACT: Context: Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. Objective: To define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. Design: GIP receptor (GIPR) expression was analysed in subcutaneous (SAT) and visceral (VAT) human adipose tissue from lean and obese subjects in three independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analysed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. Results: GIPR expression was down-regulated in SAT from obese patients and correlated negatively with BMI, waist circumference, SBP, glucose and triglyceride levels. Furthermore, HOMA-IR, glucose and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signalling in human adipocytes revealed GIP as an insulin sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 to GIPR, and decreases the association of GRK2 to IRS1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme DPP4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. Conclusions: GIP/GIPR signalling is disrupted in insulin resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.
The Journal of clinical endocrinology and metabolism 02/2014; · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is compelling evidence that obstructive sleep apnoea (OSA) can affect metabolic syndrome (MetS) and cardiovascular risk, but the intermediate mechanisms through which it occurs have not been well defined. We explored the impact of OSA in morbidly obese patients with MetS on adipokines, pro-inflammatory markers, endothelial dysfunction, and atherosclerosis markers.
We included 52 morbidly obese patients in an observational study matched for age, gender and central obesity in 3 groups (OSA-MetS, Non-OSA-MetS, and Non OSA-non-MetS). Anthropometrical, blood pressure, and fasting blood measurements were obtained the morning after an overnight polysomnography. VEGF, soluble CD40 ligand (sCD40L), TNF-α, IL-6, leptin, adiponectin, and chemerin were determined in serum by ELISA. OSA was defined as apnea/ hypopnea index ≥ 15 and MetS by NCEP-ATP III.
Cases and control subjects did not differ in age, BMI, waist circumference, and gender (43 ± 10 years, 46 ± 5 kg/m(2), 128 ± 10 cm, 71% females). The cases had severe OSA with 47 (32-66) events/h, time spent < 90% SpO2 7% (5%-31%). All groups presented similar serum cytokines, adipokines, VEGF, and sCD40L levels.
In a morbidly obese population with established MetS, the presence of OSA did not determine any differences in the studied mediators when matched by central obesity. Morbidly obese NonOSA-NonMetS had a similar inflammatory, adipokine VEGF, and sCD40L profile as those with established MetS, with or without OSA. Obesity itself could overwhelm the effect of sleep apnea and MetS in the studied biomarkers.
Salord N; Gasa M; Mayos M; Fortuna-Gutierrez AM; Montserrat JM; Sánchez-de-la-Torre M; Barceló A; Barbé F; Vilarrasa N; Monasterio C. Impact of OSA on biological markers in morbid obesity and metabolic syndrome. J Clin Sleep Med 2014;10(3):263-270.
Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 01/2014; 10(3):263-70. · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of our study was to compare bone mineral density (BMD) a year after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in age- and body mass index-matched women. In 33 morbidly obese women undergoing RYGB and 33 undergoing SG, plasma determinations of calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH) D3), and insulin-like growth factor-I (IGF-I) were made prior to and at 12 months after surgery. Dual-energy X-ray absorptiometry was performed in all patients 1 year after surgery. BMD at the femoral neck and the lumbar spine 1 year after surgery was similar in women undergoing RYGB and SG (1.01 ± 0.116 vs. 1.01 ± 0.122 g/cm(2), p = 0.993; 1.05 ± 0.116 vs. 1.08 ± 0.123 g/cm(2), p = 0.384). The percentage of patients with osteopenia and osteoporosis was not different between groups. In the linear regression analysis, age (β = -0.628, p = 0.034) and lean mass 12 months after surgery (β = 0.424, p = 0.021) were found to be the main determinants of femoral neck BMD. Age (β = -0.765, p = 0.025), menopause (β = -0.898, p = 0.033), and lean mass (β = 0.615, p = 0.023) were determinants of BMD at the lumbar spine. No influence was found between low bone mass and type of surgery, plasma PTH, 25(OH) D3, or IGF-I. The effect of RYGB and SG on BMD was comparable a year after surgery. Menopausal women were at a higher risk of having low bone mass, but the presence of osteoporosis was uncommon.
[Show abstract][Hide abstract] ABSTRACT: Morbid obesity is a serious health problem whose prevalence is increasing. Expensive co-morbidities are associated to these patients, as well as a reduction in the survival. Bariatric surgery resolves the co-morbidities (type 2 diabetes mellitus, 86.6%; cardiovascular risk, 79.0%; obstructive sleep apnea syndrome, 83.6%; hypertension, 61.7%), reduces the mortality rate (among 31-40%), and increases the morbid obese patients survival over a 10-years period. It provides significant savings for the National Health System. The obese patients consume a 20% plus of health resources and 68% plus of drugs than general population. Bariatric surgery requires an initial investment (diagnosis-related group cost: 7,468 €), but it is recovered in a cost-effectiveness ratio of 2.5 years. Significant savings are obtained from the third year. To the direct economic benefits associated with reduced health expenditures it should be added an increase in tax collection (sick leave and unemployment reduction is estimated in 18%, with a productivity increase of 57% for self-employed people). Bariatric surgery is one of the most cost-effective procedures in the healthcare system.
[Show abstract][Hide abstract] ABSTRACT: We performed an observational analysis of a prospective cohort of immunocompetent hospitalized adults with community-acquired pneumonia (CAP) to determine the epidemiology, clinical features, and outcomes of pneumonia in patients with diabetes mellitus (DM). We also analyzed the risk factors for mortality and the impact of statins and other cardiovascular drugs on outcomes. Of 2407 CAP episodes, 516 (21.4%) occurred in patients with DM; 483 (97%) had type 2 diabetes, 197 (40%) were on insulin treatment, and 119 (23.9%) had end-organ damage related to DM. Patients with DM had different clinical features compared to the other patients. They were less likely to have acute onset, cough, purulent sputum, and pleural chest pain. No differences in etiology were found between study groups. Patients with DM had more inhospital acute metabolic complications, although the case-fatality rate was similar between the groups. Independent risk factors for mortality in patients with DM were advanced age, bacteremia, septic shock, and gram-negative pneumonia. Patients with end-organ damage related to DM had more inhospital cardiac events and a higher early case-fatality rate than did the overall population. The use of statins and other cardiovascular drugs was not associated with better CAP outcomes in patients with DM. In conclusion, CAP in patients with DM presents different clinical features compared to the features of patients without DM.
[Show abstract][Hide abstract] ABSTRACT: Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in biochemical and metabolic properties, especially when obesity is present. We submitted paired SAT and VAT samples from six morbidly obese patients and six non-obese persons to two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight mass spectrometry. Compared with non-obese subjects, obese patients presented with increased carboxylesterase-1, zinc finger protein 324A, annexin A5, ubiquitin carboxyl-terminal hydrolase, α-crystallin B chain, osteoglycin, retinal dehydrogenase-1 and 14-3-3 protein γ, and decreased transferrin, complement C3, fibrinogen γ chain, albumin, α1-antitrypsin and peroxiredoxin-6, irrespective of the adipose tissue depot studied. SAT and VAT differed in protein species of fibrinogen and osteoglycin, whereas adipose tissue depot and obesity interacted on the protein abundance of actin, α-actinin 1, one protein species of carboxylesterase-1, retinal dehydrogenase-1 and 14-3-3 protein γ. Our nontargeted proteomic approach identified novel protein species that may be involved in the development of obesity in humans.
Molecular and Cellular Endocrinology 07/2012; 363(1-2):10-9. · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aims of our study were to examine the lifetime prevalence of obesity rate in eating disorders (ED) subtypes and to examine whether there have been temporal changes among the last 10 years and to explore clinical differences between ED with and without lifetime obesity.
Participants were 1383 ED female patients (DSM-IV criteria) consecutively admitted, between 2001 and 2010, to Bellvitge University Hospital. They were assessed by means of the Eating Disorders Inventory-2, the Symptom Checklist-90-Revised, the Bulimic Investigatory Test Edinburgh and the Temperament and Character Inventory-Revised.
The prevalence of lifetime obesity in ED cases was 28.8% (ranging from 5% in anorexia nervosa to 87% in binge-eating disorders). Over the last 10 years, there has been a threefold increase in lifetime obesity in ED patients (p < .001). People with an ED and obesity had higher levels of childhood and family obesity (p < .001), a later age of onset and longer ED duration; and had higher levels of eating, general and personality symptomatology.
Over the last 10 years, the prevalence of obesity associated with disorders characterized by the presence of binge episodes, namely bulimic disorders, is increasing, and this is linked with greater clinical severity and a poorer prognosis.
European Eating Disorders Review 03/2012; 20(3):250-4. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Obstructive sleep apnea is common in patients waiting for bariatric surgery (BS). International consensuses have recommended assessment of obstructive sleep apnea in the preoperative evaluation to avoid perioperative complications. Polysomnography is the standard diagnostic method but is expensive and time-consuming. The aim of our study was to detect those patients who merit treatment before BS using a simple predictor model. The study was conducted at 3 university hospitals (Hospital de Bellvitge, Hospital de la Santa Creu i Sant Pau, Hospital Clinic de Barcelona). METHODS: A prospective cross-sectional study was conducted of 136 consecutive bariatric subjects. The outcome variable was severe obstructive sleep apnea, defined as an apnea-hypoapnea index of ≥30 events/hr by polysomnography. The predictors evaluated were anthropometric and clinical in the first model, with an oxygen desaturation index of ≥3% added to the second model. Predictive models were constructed using multivariate logistic regression analysis. The best model was selected according to the area under the receiver operating characteristic curve. RESULTS: The first model identified 4 independent factors: age, waist circumference, systolic blood pressure, and witnessed apnea episodes, with a sensitivity of 78%, specificity of 68%, and area under the receiver operating characteristic curve of .83 (95% confidence interval .76-.90, P < .001). The second model identified 2 independent factors (witness apnea episodes, oxygen desaturation index of ≥3%), with a sensitivity of 91%, specificity of 85%, and area under the receiver operating characteristic curve of .94 (95% confidence interval .89-.98, P < .001). The 2-step model predictive values were sensitivity of 90%, specificity of 91%, and accuracy of 90% (95% confidence interval 84-94%). After applying the first model and then the second, 45% of subjects would have been ruled out (15% and 30%, respectively) and 55% would require additional sleep management before BS. CONCLUSION: The proposed model could be useful for improving the management of complex patients before BS and optimizing limited polysomnography resources.
Surgery for Obesity and Related Diseases 02/2012; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnoea (OSA) seems to worsen metabolism. This effect has not been evaluated in morbid obesity (MO). We hypothesised that the metabolic profile is more impaired in MO patients with OSA than in those without, and investigated whether any specific metabolic dysfunction is related to OSA in MO. A prospective multicentre cross-sectional study was conducted in consecutive subjects before bariatric surgery. OSA was defined as apnoea/hypopnoea index (AHI) ≥15 by overnight polysomnography. Anthropometrical, blood pressure (BP) and fasting blood measurements were obtained the morning after. Metabolic syndrome (MetS) was defined according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. 159 patients were studied: 72% were female and 72% had OSA. MetS prevalence was 70% in OSA versus 36% in non-OSA (p<0.001). As AHI severity increased, metabolic parameters progressively worsened, even in those without type 2 diabetes (DM2). AHI was independently associated with systolic and diastolic BP, triglycerides and the percentage of glycosylated haemoglobin (HbA1c) in the total sample, and with systolic BP, high-density lipoprotein cholesterol and HbA1c in those samples without DM2. OSA increased the adjusted odds ratio of having MetS by 2.8 (95% CI 1.3-6.2; p=0.009). In MO, OSA is associated with major metabolic impairment caused by higher BP and poorer lipid and glucose control, independent of central obesity or DM2.
European Respiratory Journal 05/2011; 38(5):1089-97. · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies that evaluate the influence of gastric bypass (RYGP) on bone mass are limited to short-term follow-up. We analysed changes in bone mineral density (BMD) three years after surgery and evaluated the main determinants of the development of bone disease. Prospective study of 59 morbidly obese white women aged 46 ± 8 years. BMD scanning using DEXA and plasma determinations of calcium, parathyroid hormone, 25-hydroxyvitamin D and insulin-like growth factor-I were made prior, at 12 months and 3 years after surgery. In the first postoperative year BMD decreased at femoral neck (FN) 10.2 % and in the lumbar spine (LS) 3.2 %, in the third year it additionally decreased 2.7 % and 3.1 %, respectively. BMD at both sites remained above the values of women of the same age. In the follow-up, 1.7 % developed osteoporosis at FN and 6.8 % at LS. Patients with bone disease were older, the percentage of women with menopause was greater in this group and had lower initial and final values of lean mass. The percentage of BMD loss at FN remained positively associated with the percentage of lean mass loss [β 0.304, p=0.045], and menopause [β 0.337, p=0.025]. Major osteoporotic fracture and hip fracture risk was low even in menopausal patients (3.1 % and 0.40 %, respectively). After RYGP menopausal women and those with greater lean mass loss are at higher risk of BMD loss but progression to osteoporosis is uncommon and the risk of fracture is low.
Obesity Surgery 12/2010; 21(4):465-72. · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyse in a cohort of healthy subjects and in a group of morbidly obese patients, we studied the association amongst 25(OH) D and plasma concentrations of adipocytokines, inflammatory cytokines and insulin resistance. We also aimed to determine whether vitamin D-deficient patients showed a greater inflammatory profile. In the observational study that the authors conducted, plasma concentrations of 25(OH) D, leptin, resistin, adiponectin and interleukine-18 were determined in 134 healthy men and 127 women. In the population consisting of 44 patients with morbid obesity, plasma concentrations of 25(OH) D, leptin, resistin, adiponectin, interleukine-18, soluble tumor necrosis factor receptors 1 and 2 and C-reactive protein were analysed. In the healthy population, plasma 25(OH) D showed a negative correlation with body mass index, body fat, waist, hip circumference and with leptin. However, no significant associations were found amongst 25(OH) D and plasma concentrations of resistin, adiponectin or interleukine-18. Patients with vitamin D deficiency showed higher body mass index, fat mass percentage and higher leptin concentrations compared with subjects with normal 25(OH) D concentrations. In the morbidly obese subjects, 25(OH) D did not correlate with leptin, resistin, adiponectin, interleukine-18, soluble tumor necrosis factor receptors 1 and 2 or with C-reactive protein. In patients with morbid obesity, no differences were found in adipokines and inflammatory cytokines concentrations regarding 25(OH) D status. No associations were found either between 25(OH) D and plasma glucose and insulin resistance or with lipid profile. Plasma 25(OH) D concentrations are associated with adiposity markers but not with adipocytokines implicated in inflammation. This lack of association does not support a major role of 25(OH) D in the pro-inflammatory environment observed in morbidly obese subjects. In addition, subjects with vitamin D deficiency are not characterized by a greater inflammatory state.
[Show abstract][Hide abstract] ABSTRACT: Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of obesity-related insulin resistance, its role in human obesity is still unclear. Our objectives were to find out the effect on RBP4 systemic levels of a weight loss induced by gastric bypass surgery and to analyze RBP4 relationships with insulin resistance, parameters of body composition, lipid metabolism, and inflammation.
Sixty-three obese women were analyzed before and 12 months after surgery of systemic concentrations of RBP4, fasting glucose, insulin, lipid profile molecules, and inflammation-related proteins (C-reactive protein, tumor necrosis factor-alpha receptors 1 and 2, interleukin-18, and adiponectin), and waist and hip circumference measurements, body mass index calculation, and insulin resistance index by homeostasis model assessment were also made.
We found that RBP4 levels were lower after weight reduction by gastric bypass surgery (p < 0.0001). We found RBP4 associated with triglycerides before (beta = 0.37, p = 0.02) and after surgery (beta = 0.59, p < 0.0001) and negatively with weight loss after surgery (beta = -0.37, p = 0.003). When expressed as a percentage of change, the decrease of RBP4 was related to the reduction in the levels of triglycerides and with the increase in HDL-cholesterol (beta = 0.73, p = 0.02 and beta = 0.62, p = 0.04, respectively). Others parameters analyzed, including inflammatory markers, were not related to RBP4.
This study shows that, in obese women and after a substantial weight loss due to bariatric surgery, RBP4 was related to weight status and lipid parameters rather than to insulin sensitivity or inflammatory markers.
Obesity Surgery 09/2010; 20(9):1258-64. · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AQP7 is considered to be the sole adipose glycerol channel, and its regulation is crucial for glycemia control.
In this work, we aimed to further characterize AQP7 in human adipose tissue in obesity and type 2 diabetes (T2D): 1) to assess AQP7 expression levels in paired abdominal adipose tissue depots (sc and visceral); 2) to relate it with gene expression of genes involved in lipid metabolism; and 3) to confirm that AQP7 is mainly expressed in the adipocytes.
We conducted a transversal study of gene expression in paired samples of sc adipose tissue (SAT) and visceral adipose tissue (VAT).
Caucasian lean and obese subjects (n = 62, matched for age and gender) and T2D subjects (n = 11, matched for age, gender, and BMI with their control group) participated in the study.
We measured AQP7 expression levels in paired SAT and VAT.
We have proved the presence of AQP7 mRNA and protein in the adipocyte rather than the stromovascular fraction of adipose tissue (P = 0.001) and in mature adipocytes when differentiated in vitro. Increased AQP7 mRNA expression levels in VAT from T2D obese subjects (P < 0.05) were found. AQP7 transcript levels ratio of SAT vs. VAT changed with the presence of obesity and T2D. Interestingly, there were positive associations between AQP7 and both lipogenic and lipolytic genes in a similar manner in both adipose depots.
Taken together, these data suggest a subtle regulation between adipose depots of the sole adipose aquaporin, AQP7, which is unbalanced in obesity and T2D.
The Journal of clinical endocrinology and metabolism 05/2010; 95(7):3470-9. · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BackgroundIn patients undergoing gastric bypass, massive weight loss and impairment of calcium intake and absorption in the duodenum
and proximal jejunum may increase the risk of bone mass loss and fractures. However, few data are available regarding the
impact of this surgery on the skeleton. The aim of our study was to examine the skeletal changes in a cohort of morbidly obese
Caucasian women during the first year after gastric bypass and to analyse the factors implicated in the development of bone
MethodsSixty-two morbidly obese white women aged 45.3 ± 8.9years were studied. Anthropometric measurements, bone mineral density
(BMD) screening using dual-energy X- ray absorptiometry and plasma determinations of calcium, phosphorus, parathyroid hormone
(PTH), 25-hydroxyvitamin D [25(OH) D3] and insulin-like growth factor-I (IGF-I) were made prior to and 12months after surgery.
ResultsA year after surgery, BMD significantly decreased at the femoral neck (10.2 ± 5.7%) and at the lumbar spine (3.2 ± 4.4%).
In the follow-up, 16.1% of women had osteopenia at the femoral neck and 19.3% at the lumbar spine, and 1.6% developed osteoporosis
at the lumbar spine. Patients with bone disease were significantly older; the percentage of women with menopause was greater
in this group and had lower initial and final values of lean mass. However, no differences in body mass index, weight loss,
fat mass, calcium, PTH, 25(OH) D3 or IGF-I values were found between groups. In the logistic regression analysis, lean mass 12months after surgery and menopause
were found to be the main determinants of osteopenia after adjusting for age with odds ratios of 0.82 and 9.13, respectively.
ConclusionsThere is a significant BMD loss at the femoral neck and lumbar spine a year after gastric bypass. Menopausal patients and
those with greater lean mass loss are at greater risk and, consequently, should be closely followed up with periodic densitometries.
Obesity Surgery 07/2009; 19(7):860-866. · 3.10 Impact Factor